Genotype-phenotype association studies may provide important prognostic information and guide therapeutic decision making in genetic disease. The phenotype of sickle cell anemia, a prototypic Mendelian single gene disorder, is notoriously heterogeneous. The diversity is likely to result from the actions and interactions of many modifying genes. Candidate disease modulating genes may regulate oxidative biology, nitric oxide metabolism, vascular function, inflammation and cell-cell interaction. Our novel observations linking polymorphisms in candidate genes with phenotypes of sickle cell anemia in African Americans and funded by the parent grant need to be expanded to another population and confirmed. Salvador, Bahia, Brazil provides an ideal site for confirmatory and additional studies. A large number of sickle cell disease patients reside in the area and a clinical and research infrastructure exists that can be refocused on genetic association studies. This work will move us closer toward applying our observations prognostically and therapeutically, while building the capacity for modern genetic studies in Salvador. Our prime objectives are: 1) developing a sickle cell disease patient registry, database and DNA sample repository of sickle cell disease patients from Salvador Bahia, Brazil. 2) genotyping single nucleotide polymorphisms (SNPs) in candidate genes in Brazilian patients in Bahia. These results will be compared with our findings in African Americans providing information on the similarities and differences in modulating genes in geographically distinct populations. 3) training Brazilian investigators in state-of-the-art methods of analysis of large complex data sets while continuing to refine methods for using polymorphisms in prognostically useful interactive networks. Our results will also prepare Brazilian investigators to collaborate with us in a new NIH Sickle Cell Disease Clinical Research Network. [unreadable] [unreadable] [unreadable]